It has been shown in recent years that proteolytic enzymes of the sperm acrosome play a significant role in the fertilization process in rabbits and other animals. There is evidence that inhibition of acrosomal proteases interfere with the fertilization process. Proteolytic enzymes in seminal fluid may also be involved in sperm penetration through the mucoid secretions of the female genital tract. It is the objective of this research proposal to isolate and characterize the proteolytic enzymes from the sperm and seminal plasma of the human and the rhesus monkey, to study their origins and their role in the reproductive process and the interaction with inhibitors and immune antibodies. Since experimentation in human reproductive biology is rather difficult if not impossible, a considerable part of reproductive research has to rely on experimentation with subhuman primates because of certain similarities. Comparative studies between the human and the rhesus monkey proteases in sperm and seminal fluid would increase the potential usefulness of rhesus monkeys as experimental animals in fertility control research. Acrosomal proteases and seminal fluid proteases will be extracted and isolated from human and rhesus monkey ejaculates according to previously described methods. The enzymes will be characterized and their activity against synthetic low molecular weight substrate and against nonspecific macromolecular and specific biological substrates such as the outer layer of the ovum and cervical mucus will be determined. The interference of synthetic and natural inhibitors and of immune antibodies will be studied to characterize the enzymes further and to study possible ways of interference with reproductive processes. The proposed studies therefore not only promise to give a much clearer understanding of the reproductive processes in humans and subhuman primates but will lead to potential antifertility measures or agents that are nonhormonal in origin.